Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model.

Barry Rockx1 Thijs Kuiken2 Sander Herfst2 Theo Bestebroer2 Mart M Lamers2 Bas B Oude Munnink2 Dennis de Meulder2 Geert van Amerongen3 Judith van den Brand2 Nisreen M A Okba2 Debby Schipper2 Peter van Run2 Lonneke Leijten2 Reina Sikkema2 Ernst Verschoor4 Babs Verstrepen4 Willy Bogers4 Jan Langermans5,6 Christian Drosten7 Martje Fentener van Vlissingen8 Ron Fouchier2 Rik de Swart2 Marion Koopmans2 Bart L Haagmans1
Affiliations 8 institutions
  1. Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands. [email protected] [email protected].
  2. Department of Viroscience, Erasmus University Medical Center, Rotterdam, Netherlands.
  3. Viroclinics Xplore, Schaijk, Netherlands.
  4. Department of Virology, Biomedical Primate Research Centre, Rijswijk, Netherlands.
  5. Animal Science Department, Biomedical Primate Research Centre, Rijswijk, Netherlands.
  6. Population Health Sciences, Unit Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Netherlands.
  7. Institute of Virology, Charité-Universitätsmedizin, Berlin, Germany.
  8. Erasmus Laboratory Animal Science Center, Erasmus University Medical Center, Rotterdam, Netherlands.

Abstract

The current pandemic coronavirus, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (COVID-19). To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)-CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19-like disease in macaques and provides a new model to test preventive and therapeutic strategies.

Supporting text Virus Host Location
Disease Models, Animal 77 Macaca fascicularis 10 Aging 4 Animals 1948 Betacoronavirus 78 Coronavirus Infections 171 COVID-19 425 Female 289 Lung 65 Middle East Respiratory Syndrome Coronavirus 68 Pandemics 108 Pneumonia, Viral 42 Pulmonary Alveoli 3 Respiratory System 21 SARS-CoV-2 453 Severe Acute Respiratory Syndrome 22 Severe acute respiratory syndrome-related coronavirus 78 Virus Replication 191 Virus Shedding 51

Evidence records

1 total
Experimental Infection
1 records · 1 evidence types
Evidence type
1 records
OVE11562
Key finding

Experimental infection of cynomolgus macaques with MERS-CoV produced milder lung lesions than SARS-CoV infection, with virus localized mainly in type II pneumocytes.

Virus
Host
Location
Not specified
Supporting text

We inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)-CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes.

Method
experimental infection | histopathology of lung lesions | detection of virus in lung tissue
Experimental system
cynomolgus macaque animal infection model